New Data Supporting Cladribine Tablets as a Potential New Therapeutic Option Presented at the 62nd AAN Annual Meeting (1

TORONTO and GENEVA, April 16, 2010 /PRNewswire/ -- Merck Serono, a division of Merck KGaA, Darmstadt, Germany, today announced that new data providing further understanding on Cladribine Tablets as a potential new therapeutic option for relapsing forms of multiple sclerosis (MS) were presented at the 62nd Annual Meeting of the American Academy of Neurology (AAN). Cladribine Tablets, Merck Serono's proprietary investigational oral formulation of cladribine, is currently under regulatory review in a number of countries.

"The relevance of the CLARITY study is further substantiated by the series of additional analyses presented at AAN", said Bernhard Kirschbaum, Merck Serono's Head of Global Research and Development. "We are committed to continuing to work with regulatory authorities to bring Cladribine Tablets to patients at the earliest point in time."

The data presented at AAN are from pre-specified and post-hoc analyses of the Phase III CLARITY a clinical trial and show that the administration of Cladribine Tablets in study subjects resulted in:

    
    - Increase in the proportion of patients with disease activity-free
      status compared with the placebo group over the entire 96-week study
      (43% and 44% of patients treated with Cladribine Tablets total dose
      of 3.5 mg/kg and 5.25 mg/kg respectively compared with 16% of patients
      who received placebo - p<0.001 for both Cladribine Tablets groups) with
      statistically significant findings as early as 24 weeks (67% and 70%
      of patients treated with Cladribine Tablets total dose of 3.5 mg/kg and
      5.25 mg/kg respectively compared with 39% of patients who received
      placebo - p<0.001 for both Cladribine Tablets groups). Disease
      activity-free status was defined as having no clinical activity (no
      relapse and no sustained disability progression) and no radiological
      activity (no T1 Gd+ lesions and no active T2 lesions) over the
      96-week study(1)
.
    - Reductions in annualized relapse rate (ARR) compared to the placebo
      group over 96 weeks across the spectrum of baseline demographics and
      disease characteristics included in the CLARITY study (gender, age,
      treatment history, number of relapses in the 12 months preceding study
      entry, baseline disease disability, baseline MRI activity and burden
      of disease)(2)
    - Reduced consumption of healthcare resources, a decreased need for
      societal support, improvements in patient productivity, and reductions
      in total non-drug expenditure, relative to placebo, as measured by
      data collected in the CLARITY study with a 'resource utilization form'
      at baseline and at scheduled patient visits(3)
.
    - Decrease of proportions of circulating CD4+ T cells relative to the
      total number of lymphocytes at the end of treatment periods compared
      to baseline, while the proportions of other lymphocyte subtypes
      (CD8+ T, B and natural killer cells) were preserved or increased
      relative to total lymphocytes.(4)

Overall, the frequencies of adverse events by MedDRA System Organ Class in both Cladribine Tablets treatment groups from the CLARITY study were comparable to those observed in the placebo group. The most commonly reported adverse events were headaches, upper respiratory tract infection, nasopharyngitis and nausea. Lymphopenia, an expected event based on the presumed mechanism of action of cladribine, occurred more frequently in the Cladribine Tablets treatment groups (3,5 mg/kg total dose: 21.6%; 5.25 mg/kg total dose: 31.5%; placebo: 1.8%). The overall rate and incidence of infections in patients treated with Cladribine Tablets and placebo were similar. Herpes zoster infections were reported in 2.3% of patients treated with Cladribine Tablets. These herpes infections were localized to the skin and responded appropriately to treatment.

(a) CLARITY: CLAdRIbine Tablets Treating MS OrallY

References:

(1) Analysis of Clinical and Radiological Disease Activity-Free Status in Patients with Relapsing-Remitting Multiple Sclerosis (RRMS) Treated with Cladribine Tablets, in the Double-Blind, 96-Week CLARITY Study (presentation S21.008, Wednesday, April 14, 2010, 3:45 pm EDT)

(2) Consistent Efficacy of Cladribine Tablets across Multiple Sclerosis and Patient Characteristics, in the Double-Blind, 96-Week CLARITY Study (poster P02.186, Tuesday, April 13, 2010, 3:00 pm-7:30 pm EDT)

Reductions in the annualized relapse rate (ARR) across the various patient strata:

    
    - Gender (man or woman): Relative reductions in ARR were 61% and 55%,
      respectively, for 3.5 mg/kg and 68% and 48%, respectively, for
      5.25 mg/kg (all p<0.001 versus placebo)
    - Age (=40 or >40): Relative reductions in ARR were 58% and 57%,
      respectively, for 3.5 mg/kg and 63% and 46%, respectively, for
      5.25 mg/kg (all p<0.001 versus placebo)
    - Treatment history (previously treated with disease-modifying therapy
      or drug-naïve patients): Relative reductions in ARR were 45% and 61%,
      respectively, for 3.5 mg/kg and 58% and 58%, respectively for
      5.25 mg/kg (all p=0.0013 versus placebo)
    - Number of relapses in the 12 months preceding study entry (=1, 2 or
      =3 relapses): Relative reductions in ARR ranged from 48% (relative
      risk: 0.50; 95% confidence interval: 0.37, 0.66) to 76% (relative
      risk: 0.24; 95% confidence interval: 0.09, 0.64) depending on dose
      group (all p=0.006 versus placebo)
    - Level of disability at baseline (EDSS 0-2.5 or EDSS =3): Relative
      reductions in ARR ranged from 49% (relative risk: 0.51; 95%
      confidence interval: 0.38, 0.68) to 65% (relative risk: 0.35; 95%
      confidence interval: 0.25, 0.50) depending on dose group (all p<0.001
      versus placebo)
    - T1 Gd+ lesions (no lesions or =1 lesion): Relative reductions in ARR
      ranged from 45% (relative risk: 0.55; 95% confidence interval: 0.42,
      0.72) to 75% (relative risk: 0.26; 95% confidence interval: 0.17, 0.40)
      depending on dose group (all p<0.001 versus placebo)
    - T2 lesion volume (>or = median T2 lesion volume status): Relative
      reductions in ARR ranged from 48% (relative risk: 0.53; 95% confidence
      interval: 0.39, 0.71) to 67% (relative risk: 0.33; 95% confidence
      interval: 0.24, 0.47) depending on dose group (all p<0.001
      versus placebo)

(3) Health Resource Utilization in the CLARITY Study (poster P01.205, Tuesday, April 13, 2010, 7:30 am-12:00 pm EDT)

(4) Effects of Cladribine Tablets on Circulating Lymphocyte Subsets in the 96-Week CLARITY Study in Relapsing-Remitting Multiple Sclerosis (RRMS) (poster P04.219, Wednesday, April 14, 2010, 3:00 pm-7:30 pm EDT)

CLARITY study design

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